Research has consistently demonstrated that child maltreatment places children at heightened risk for the emergence of psychopathology, including major depressive disorders (MDD;Cicchetti &Valentino, 2006;Thompson, 2005;Widom et al., 2007). Adolescents with maltreatment histories have been found to be three times more likely to become depressed or suicidal than adolescents without histories of maltreatment (Brown et al., 1999). Because adolescence represents a peak time for the emergence of depressive disorders, as well as a developmental period during which rates of depression for girls begin to exceed those of boys, the provision of preventive intervention for adolescent girls with elevated depressive symptoms is particularly important. Moreover, because studies examining processes underlying depression have begun to elucidate differential pathways based on the presence of maltreatment (Heim et al., 2008), the evaluation of a preventive intervention for subsyndromal depressed adolescent girls with or without histories of maltreatment addresses a critical gap in the prevention literature. As increased knowledge on the biological consequences of child abuse and neglect has emerged (Watts-English et al., 2006), it is increasingly important to incorporate a multiple- levels-of-analysis perspective into the design and evaluation of preventive interventions. The proposed research seeks to extend knowledge on an efficacious preventive intervention for depression in adolescent girls with and without histories of maltreatment. The investigation will utilize a developmental psychopathology framework with 350 low-income ethnically and culturally diverse adolescent girls to evaluate the efficacy of Interpersonal Psychotherapy for Adolescents (IPT-A) for preventing depression. 140 of these adolescents with depressive symptoms will have histories of child maltreatment and 140 will be demographically comparable but without maltreatment history. Within each group, half will be randomly assigned to IPT-A and half to enhanced care with comparable duration. An additional group of 70 nonmaltreated nonsymptomatic girls will serve as a comparison for to determining how psychological and neurobiological functioning in the depressive groups may approximate that seen in a nonsymptomatic group of adolescents. The investigation will apply a multiple- levels-of-analysis approach to evaluate IPT-A efficacy in decreasing depressive symptoms and preventing MDD in maltreated and nonmaltreated adolescent girls through examining genetic, neuroendocrine, cognitive, and interpersonal domains at baseline, mid-treatment, post-treatment, and at one-year follow-ups. Group differences in the network of causative processes in depression for maltreated and nonmaltreated adolescents will be examined in relation to outcomes. Additionally, potential mechanisms involved in the intervention process will be examined, including changes in neuroendocrine regulation, cognitive processes, and interpersonal relations. Additionally, analyses will determine whether genetic differences moderate the efficacy of IPT-A in reducing depressive symptomatology in maltreated and in nonmaltreated girls. PUBLIC HEALTH RELEVANCE: Investigations comparing maltreated youth with demographically similar youth have found that abuse and neglect increase risk for the development of subsequent psychopathology, including depression. The proposed investigation will apply a multiple- levels-of-analysis approach to evaluating the efficacy of Interpersonal Psychotherapy for Adolescents (IPT-A) efficacy in reducing depressive symptoms and preventing Major Depressive Disorder in low-income culturally diverse maltreated and nonmaltreated adolescent girls through examining genetic, neuroendocrine, cognitive, and interpersonal domains at baseline, mid-treatment, post-treatment, at a one-year follow-up, and depressive symptoms will be further assessed at an 18-month follow-up. Given the paucity of evidence-based preventive interventions for depression associated with maltreatment, and the utilization of a multiple-levels-of-analysis of intervention effects, the provision and evaluation of IPT-A to low-income culturally diverse girls with and without histories of child maltreatment is particularly important and innovative and possesses very high public health significance.